Method for macrocyclic lactones

ABSTRACT

MACROCYCLIC COMPAOUNDS ARE PRODUCED WHEN CYCLIC KETONE DI- AND TRIPEROXIDES ARE DECOMPOSED BY IRRADIATION WITH ULTRAVIOLET LIGHT OR BY HEATING TO A REMPERATURE ABOVE 100*C.

3,776,926 METHOD FOR MACROCYCLIC LACTONES Paul R. Story, Athens, Ga.,assignor to Research Corporation, New York, N.Y. No Drawing. ApplicationJan. 9, 1970, Ser. No. 10,121,

now Patent No. 3,584,067, which is a division of application Ser. No.697,593, Jan. 15, 1968, now Patent No. 3,528,898. Divided and thisapplication Nov. 24, 1970, Ser. No. 92,546

Int. Cl. C07d 9/00 US. Cl. 260343 5 Claims ABSTRACT OF THE DISCLOSUREMacrocyclic compounds are produced when cyclic ketone diand triperoxidesare decomposed by irradiation with ultraviolet light or by heating to atemperature above 100 C.

This application is a divisional application of my application Ser. No.10,121, filed Jan. 9, 1970, and now US. Pat. No. 3,584,067, which is adivisional application of my application Ser. No. 697,593, filed Jan.15, 1968, and now U.S. Pat. No. 3,528,898.

This invention relates to a method for the preparation of macrocycliccompounds. In one specific aspect, it relates to a method for thepreparation of macrocyclic hydrocarbons and macrocyclic lactones.

It is known that dimeric and trimeric peroxides are formed by the actionof hydrogen peroxide on cyclic ketones such as cyclohexanone. I have nowdiscovered that the thermal or ultraviolet light induced decompositionof such peroxides yields macrocyclic hydrocarbons and/ or macrocycliclactones.

Accordingly, it is a principal object of the present invention toprovide a convenient method for the preparation of macrocyclichydrocarbons and macrocyclic lactones. This and other objects andadvantages of the invention will become apparent on consideration of thediscussion and examples which follow:

The dimeric and trimeric peroxides used in practicing the presentinvention are prepared as described in the literature:

Diperoxides.--R. Criegee et al., Ann., 583, 6 (1953); M. S. Kharasch etal., J. Org. Chem., 23, 1322 (1958); T. Ledaal, Acta Chem. Scand., 21,1656 (1967).

Triperoxides.R. Criegee et al., Ann., 565, 7 (1949); W. Dilthey et al.,J. prakt. Chem., 154, 219 (1940).

In one embodiment of my invention, the reactant peroxide is decomposedthermally, for example, by heating in a sealed tube to a temperatureabove 100 C. or, more preferably, by direct injection into a heatedchromatographic column, or heated packed column of a standard pyrolysistype. In a second embodiment of my invention, the reactant peroxide,usually dissolved in a suitable organic solvent, is decomposed byirradiation with ultraviolet light from a mercury lamp or otherconvenient source.

The diperoxides decompose according to the overall equation:

8 (011mb 1m. (out),

The diperoxide reactants are derived from cyclic ketones characterizedby the presence of a S-membered or larger (CH2)b nited States Patent Dice ring. Thus, b is an integer greater than 3 in the above equation.

The triperoxides decompose according to the equation:

(H E C s (011mb I)3b M The triperoxide reactants are also derived ctromcyclic ketones characterized by the presence of a S-rnembered or largerring and b is again an integer greater than 3.

Whereas both hydrocarbons and lactones are generally produced ondecomposition of the peroxide reactants, the hydrocarbon usuallypredominates when ketone triperoxides are thermally decomposed. Witheither dior triperoxides, a portion of the cyclic ketone used to preparethe peroxide reactant is usually recovered as a by-product of thedecomposition reaction.

EXAMPLE 1 Decomposition of diperoxide Caution: Peroxides mayoccasionally explode with considerable violence. It a small amount ofsolvent such as methanol or benzene is allowed to remain with the solidperoxides, explosions can generally be avoided.

(A) Five grams of cyclohexanone diperoxide was sealed under vacuum intoa milliliter ampoule and the ampoule heated at C. for 30 minutes. Aftercooling to room temperature, the contents of the ampoule (now liquid)were separated and purified by preparative gas chromatography using acolumn of 20% silicone polymer on diatomaceous earth. There was obtained1.17 gram (44% yield) of cyclodecane and 0.80 gram (23% yield) ofll-undecanolactone. About 21% of the diperoxide reactant was recoveredas cyclohexanone. Similar results were obtained by injectingcyclohexanone diperoxide into a variety of chromatographic columns at C.

(B) Twelve grams of cyclohexanone diperoxide dissolved in 4.5 liters ofmethanol (or benzene) was irradiated with ultraviolet light for 3 hoursusing a standard quartz Hanovia apparatus with a 450 watt lamp. Afterevaporation of the solvent using a rotary evaporator followed bychromatographic separation, there was obtained a 14% yield ofcyclodecane and a 9% yield of 11- undecanolactone. About 20% of thediperoxide reactant was recovered as cyclohexanone.

(C) Using an approach similar to that employed in part (A), thermaldecomposition of cycloheptanone diperoxide gave a 22% yield ofcyclododecane and less than 1% of 13-tridecanolactone. About 33% of thediperoxide reactant was recovered as cycloheptanone.

(D) Using an approach similar to that employed in part (B),cycloheptanone diperoxide gave a 32% yield of cyclododecane and 7% ofthe lactone on irradiation with ultraviolet light. About 24% of thediperoxide reactant was recovered as cycloheptanone. A similar thermaldecomposition of cyclododecanone diperoxide gave a 20% yield ofcyclodocosane, 11% of 23-tricosanolactone and 9% of cyclododecanone.

EXAMPLE 2 Decomposition of triperoxides (A) A solution containing 12grams of cyclohexanone triperoxide in 4.5 liters of methanol wasirradiated with ultraviolet light for 3 hours in a quartz apparatususing a 450 watt Hanovia lamp. The solvent was removed using a rotaryevaporator and the product separated and purified by preparative gasphase chromatography. There was obtained 1.1 grams (15% yield) ofcyclopentadecane, and 2.2 grams (25% yield) of 16-hexadecanolactone,also known as dihydroambrettolide. About 20% of the triperoxide reactantwas recovered as cyclohexanone.

(B) Thermal decomposition of cyclohexanone triperoxide at 150 C. gave a16% yield of cyclopentadecane and less than 1% of l6-hexadecanolactone.About 15% of the reactant triperoxide was recovered as cyclohexanone.

(C) Cyclopentanone triperoxide was thermally decomposed in a similarfashion to give a 20% yield of cyclododecane and a 2% yield of13-tridecanolactone. About 24% of the triperoxide reactant was recoveredas cyclopentanone. In this and the other examples given above, theidentity of the reaction products isolated and confirmed by infrared,N.MJR. and mass spectral analyses.

The process of the present invention provides a method for thepreparation of macrocyclic lactones of the musk compound type useful inperfumes. P. Z. Bedoukian, Amer. Perf. Cosmet., 80, 23 (1965), P. Z.Bedoukian Perfumery Synthetics and Isolates, D. Van Nostrand, New York(1951).

The process of the present invention also provides a method for thepreparation of macrocyclic hydrocarbons useful in the preparation ofhighly desirable musk ketones. For example, cyclopentadecane can bechlorinated or brominated in the presence of light, the resultantcyclopentadecanyl chloride or bromide hydrolyzed with weak alkali tocyclopentadecanyl alcohol, and the alcohol oxidized with dichromate tocyclopentadecanone, a compound having pure musk odor.

While the process of the present invention has been described withparticular reference to the use of carbocyclic ketone peroxides as thereactants, the preparative reaction is also effective using heterocyclicketones peroxides to make heterocyclic compounds, i.e., cyclic compoundswherein one or more of the methylene groups is replaced by a heteroatomsuch as oxygen. One or more methylene groups of the carbocyclic orheterocyclic ketone peroxide reactant may bear substituent groups suchas hydroxy, halo, alkoxy, acyloxy, amido, amino or carboxyl, or alkyl oraryl groups bearing such substituent groups. When the substituentsconsist of hydroxy, carboxy, amino, hydroxyalkyl, carboxyalkyl,aminoalkyl, hydroxyaryl, carboxyaryl or aminoaryl groups, the resultantpolyfunctional macrocycle is useful in the preparation of desirableelastomeric polyesters and polyamides.

The decomposition of substituted ketone peroxides according to themethod of the present invention provides an alternate approach to thepreparation of desirable musk compounds such as cyclopentadecanone. Forexample, the carbonyl groups (or a group capable of conversion to thecarbonyl group or other desired group) can be built into the peroxidereactant prior to its decomposition as illustrated below:

Cyelopentadecanone Other variations falling within the scope of thepresent invention will suggest themselves to those skilled in the artand my invention is as claimed.

The work on which this application was based was financed in whole or inpart by the Department of Health, Education, and Welfare. I

I claim:

1. A method for the preparation of macrocyclic lactones of the formula:

wherein a is 2 or 3 and b is greater than 3 which comprises decomposingdiand triperoxides of the formula:

References Cited UNITED STATES PATENTS 3,546,251 12/1970 Matsumoto et a1260343 JOHN M. FORD, Primary Examiner US. Cl. X. R.

